Dyskeratosis congenita (DKC)

2001-08-01   Claude Viguié 

Identity

Name

Dyskeratosis congenita (DKC)

Alias

Zinsser Cole Engeman syndrome , Hoyeraal Hreidarsson syndrome

Note

Hoyeraal Hreidarsson syndrome is a more severe variant

Inheritance

X-linked recessive form constitute more than 80% of cases and 91% of DKC patients are males

Omim

127550 , 224230 , 305000 , 613987 , 613988 , 613989 , 613990 , 615190 , 616353

Mesh

D019871

Orphanet

1775 Dyskeratosis congenita

Umls

C0265965

Clinics

Phenotype and clinics

  • Short stature (16%)
  • Cutaneous signs:
    Hyperpigmentation, telangiectasia, atrophy (poïkilodermia)
    Dystrophic nails and palmoplantar keratoderma , hyperhidrosis
    Mucosal leucoplakia
    Dental caries or loss ( 18%)
    Blepharitis, conjunctivitis, epiphora (36%)
    Sparse eyebrows \/ eyelashes
    Alopecia (16%)
    Urethral stricture, phimosis (7%)
  • Bone marrow failure, peripheral pancytopenia ( 93%)
  • Others signs:
    Oesophageal stricture (14%)
    Pulmonary fibrosis (19%)
    Liver cirrhosis (5%)
    Hypogonadism (8%)
    Abnormal bone trabeculation, osteoporosis (4%)
  • Immune abnormalities: reduced or increased immunoglobulin level, T- and\/or B-lymphocyte deficiency.
  • Mild Mental Retardation, learning difficulties (21%)
    • Atlas Image
    leucokeratosis of the tongue, poïkilodermia of the foot and the trunk, onychopathy. Courtesy Daniel Wallach

    Prognosis

  • The major part of patients di before 20 years, mainly from infectious complications of immune deficiency.
  • 90% of patients have haematological abnormalities when 30 year-old , and bone marrow failure is the main cause of early morbidity in 71% of cases. It can evolve toward aplastic anemia or myelodysplasia.
  • The mucosal leucoplakia can transform into spinocellular carcinoma.
  • Other carcinomas can develop during the third decade of life: lung, colon, larynx, oesophagus, pancreas, Hodgkin disease.

    • Cytogenetics

    Inborn condition

    An excess of chromosome breakages has been reported in DKC but this finding is controversial; not frequently, rearrangements comparable to what is observed in Fanconi anemia are described: chromosome instability and breakage (di- and tricentric chromosomes), either spontaneous or induced by clastogenic agents (mitomycin C). Cells with a high turn-over (skin fibroblasts, lymphocytes, bone marrow cells, digestive tract) would be particularly sensitive to chromosome rearrangements and DNA damage.

    Genes involved and Proteins

    Description

    DKC1 encodes for Dyskerin, a 514 aminoacid protein

    Expression

    widespread tissue repartition

    Function

    Dyskerin is the nucleolar pseudouridine synthetase component of the box H+ACA snoRNAs. It also interacts with the RNA component of human telomerase. Chromosome instability could be linked to increased telomere shortening due to an alteration in telomerase-dependant telomere maintenance. DKC1 plays a role in ribosomal RNA synthesis and in ribosome biogenesis; DKC is a human ribosomopathy.

    To be noted

    Hgmd

    119096

    Bibliography

    Pubmed IDLast YearTitleAuthors